The present invention relates to polymerizable acrylophosphonic acids which have a high hydrolysis stability and are suitable in particular for preparing, or as components of, polymers, adhesives or other materials and mainly dental materials.
Polymerizable phosphonic acids are of polymer-chemical importance mainly as comonomers. They allow the preparation of organic polymers with high thermal stability, good adhesion properties, high ignition temperature and good solubility in polar solvents. For this purpose, numerous monomeric phosphonic acids with polymerizable vinyl, dienyl, allyl, or styryl groups have been synthetized and polymerized. An overview of phosphonic acids is given by Houben-Weyl, Methoden der Organischen Chemie, Vol. E 20 (2nd part), Georg Thieme Verlag, Stuttgart-New York 1987, p. 1300 et seq). Examples of such conventional polymerizable phosphonic acids are vinyl phosphonic acid, allylbenzene phosphonic acid, xcex1-aminoallyl phosphonic acid, phenylethene phosphonic acid, 1,3-butadiene or isoprene phosphonic acid, 4-vinylbenzene phosphonic acid or 2-(4-vinylphenyl)-ethane phosphonic acid.
Phosphonic acids in which the Cxe2x95x90C group is bound to the phosphorus atom directly or via an oxygen atom, such as e.g. vinyl phosphonic acid or ethyl phosphonic acid monovinyl ester, show at most only a moderate tendency towards homopolymerization, so that only homopolymers with a low molecular weight are accessible.
High-molecular-weight polymerisates can on the other hand be obtained from (meth)acrylophosphonic acids or esters in which the (meth)acrylic group is not bound directly to the phosphorus, but via a hydrolysis-stable spacer group. Such (meth)acrylophosphonic acid derivatives are described for example in DE-B-27 11 234.
DE-A-32 10 775 discloses 2-acrylamido-2-methyl-propane phosphonic acid with the formula CH2xe2x95x90CHxe2x80x94CONHxe2x80x94C(CH3)2xe2x80x94CH2xe2x80x94P(xe2x95x90O)(OH)2 as well as its use for preparing copolymerides.
DE-A-33 13 819 and JP 62-63314 (Chem. Abstr. 107 (1987), 41318f) disclose methacrylic acid-(2-phosphono-1,1-dimethylethylamine) of the formula CH2xe2x95x90C(CH3)xe2x80x94CONHxe2x80x94C(CH3)2xe2x80x94CH2xe2x80x94P(xe2x95x90O)(OH)2.
According to EP-B-0 089 654 and U.S. Pat. No. 4,650,591 acrylic acid-(2-phosphono-1,1-dimethylethylamine), also called 2-acrylamido-2-methylpropylhosphonic acid, is suitable as a corrosion inhibitor in the form of its homo- or copolymers.
DD-A-273 846 discloses adhesion promoters based on N-acyl-aminomethan-bisphosphonic acid derivatives.
These known (meth)acrylophosphonic acid derivatives are not stable in aqueous solution. Rather, they show, a hydrolytic clearage of the (meth)acrylic group which is even catalyzed by dissociated protons of the phosphonic acid group and thus accelerated.
The use of aqueous solutions is however advantageous or absolutely necessary in a whole series of applications of polymerizable phosphonic acids. This is the case e.g. in the preparation of low viscosity adhesives which are free from organic solvents, or in dental adhesives which lead to an optimal wetting of the moist dentine surfaces only in aqueous form.
DE 197 46 708 A1 discloses polymerizable acrylophosphonic acids which are hydrolysis-stable in an aqueous solution, have good adhesion properties, can be polymerized with conventional radical initiators and are therefore suitable as a component in particular of adhesives, molded articles, cements or composites and in particular dental materials. The acrylophosphonic acids show a good solubility, in the form of their carboxylic acid esters, in water and polar organic solvents, whereas in the form of carboxylic acids they are easily soluble in water but hardly soluble in organic solvents. The different dissolving behaviour of ester and acid can be disadvantageous in the case of aqueous materials. The hydrolysis of the carboxylic acid esters to produce free carboxylic acid and alcohol can significantly change the solubility of the monomers and thus lead to partial or complete precipitation of the phosphonic acid component and thus influence the properties of the material.
The object of the invention is the preparation of polymerizable acrylophosphonic acids which are practically completely hydrolysis-stable in the presence of water at room temperature.
Surprisingly, this object was achieved by acrylophosphonic acids of the following general formula (I) 
in which R1, R2, R3, X, Y, Z and n have the following meanings:
R1=a linear or branched C1 to C10 alkylene or C6 to C14 arylene radical;
R2=hydrogen, a linear or branched C1 to C10 alkyl or C6 to C10 aryl radical;
Y=oxygen, sulphur, C1 to C8 alkylene or is absent;
n=1, 2, 3, 4, or 5;
where
X=CN, n=1 and Z=absent or
X=CONR3 with
R3=hydrogen, a linear or branched C1 to C10 alkyl radical or a C6 to C10 aryl radical;
provided that
for n=1
Z=hydrogen or a linear or branched C1 to C10 alkyl radical or a phenyl radical; and
for n=2 to 5
Z=an aliphatic, aromatic or araliphatic, linear or branched hydrocarbon radical with 1 to 14 carbon atoms, substituted n times with the structure of formula (I) in brackets, when Z and R3 may also be a part of a common ring, and when
the individual radicals may be substituted or unsubstituted.
The individual alkyl, aryl, alkylene, arylene, phenyl, phenylene and arylene alkylene radicals can be substituted by one or more substituents, such as Cl, Br, CH3O, OH, COOH, CN, xe2x95x90O, xe2x95x90S, xe2x95x90NR2 or xe2x80x94NR3xe2x80x94COxe2x80x94C(xe2x95x90CH2)CH2xe2x80x94Yxe2x80x94R1xe2x80x94PO(OH)2.
The nitriles (Xxe2x95x90CN) can be transformed into the amides (Xxe2x95x90CONR3) and can therefore be regarded as their precursors.
Further, there are preferred definitions for the above mentioned variables of the formula (I) which, unless otherwise stated, can be chosen independently from each other and are as follows:
R1=a linear or branched C1 to C5 alkylene radical or phenylene;
R2=hydrogen or a linear C1 to C3 alkyl radical;
Y=oxygen or is absent;
X=CN or CONR3 with
R3=hydrogen, a linear C1 to C6 alkyl radical, a phenyl radical or together with Z part of a six-membered ring;
n=1 or 2;
Z=hydrogen or a linear or branched C1 to C10 alkyl radical, a phenyl radical or together with R3 part of a six-membered ring (for n=1); and
Z=a linear C1 to C10 alkylene radical or together with R3 part of a six-membered ring (for nxe2x89xa72).
Particularly preferred meanings which can also be chosen independently of each other are:
R1=a linear or branched C1 to C4 alkylene radical;
R2=hydrogen or a methyl radical;
Y=oxygen;
X=CONR3;
R3=hydrogen or a linear C1 to C5 alkyl radical;
Z=hydrogen or a linear C1 to C6 alkyl radical (for n=1); and
Z=a linear C1 to C5 alkylene radical (for nxe2x89xa72).
The radicals R1, R2, R3 and/or Y are preferably unsubstituted, the radical Z is preferably unsubstituted or substituted by xe2x95x90O, xe2x95x90S, xe2x95x90NR2 or xe2x80x94NR3xe2x80x94COxe2x80x94C(xe2x95x90CH2)CH2xe2x80x94Yxe2x80x94R1xe2x80x94PO(OH)2.
Preferred compounds are those where at least one, more preferably all, of the variables of formula (I) have the preferred definitions described above, the formula (I) including all the stereoisomers possible through the named substituents and their mixtures, such as racemates.
The acrylophosphonic acids according to the invention of formula (I) (Xxe2x95x90CN, Z is absent) can be prepared by reacting alkylphosphonic acid esters APE xcex3-functionalized at the alkyl radical (R2=alkyl) with xcex1-halogen methylacryl nitrites (U=halogen, preferably Cl or Br) HMAN and subsequent elimination of the alkyl groups R2 using methods known from organic chemistry for preparing Cxe2x80x94Cxe2x80x94, Cxe2x80x94Oxe2x80x94 or Cxe2x80x94Sxe2x80x94 bonds (cf. C. Weygand, G. Hilgetag, Organisch-chemische Experimentierkunst, Johann Ambrosius Bart Verlag, Leipzig 1970, pp. 963 et seq, 362 et seq, and 657 et seq). The protection groups technique is used for the two phosphonic acid groups, i.e. the reactions e.g. are carried out with the corresponding phosphonic acid esters, from which the mono- (R2=alkyl) or dihydrogen phosphonic acids (R2=H) of formula (I) are subsequently released, depending on the hydrolysis reagent used: 
Specifically, the reaction of xcex1-chloromethylacrylnitrile with 2-hydroxyethylphosphonic acid dimethylester via 2-[4-(dimethoxyphosphoryl)-2-oxybutyl]-acrylonitrile gives, after silylation with trimethylsilyl bromide and desilyation with methanol, the corresponding phosphonic acid {2-[4-(dihydroxyphosphoryl)-2-oxabutyl]-acrylonitrile}: 
The xcex1-halogen methylacrylonitriles HMAN are accessible by reacting acrylonitrile with formaldehyde in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) and subsequent halogenation with inorganic acid chlorides, such as SOCl2, PCl3 or PBr3 (cf. DE-OS 34 44 098 and G. F. Meijs, E. Rizzardo, S. H. Thang, Polym. Bull.24 (1990) 501).
For example, the reaction of acrylonitrile with formaldehyde via xcex1-hydroxymethylacrylonitrile leads, after chlorination with thionyl chloride, to xcex1-chloromethylacrylonitrile: 
Suitable phosphonic acid esters APE can be obtained in different ways. A particularly suitable reaction for the preparation of alkanephospohonic acid esters is the Michaelis-Arbuzow reaction (cf. G. M. Kosolapoff, Org. Reactions 6 (1951) 273), where trialkyl phosphites, e.g. triethyl phosphite, and alkyl halides are reacted with each other e.g.: 
Specifically, upon the reaction of triethyl phosphite with 2-bromoethanol the 2-hydroxyethylphosphonic acid diethyl ester forms: 
The Y substituent must also be protected where appropriate. A further possibility for the synthesis of hydroxyalkylphosphonic acid esters (YHxe2x95x90OH) comprises the base-catalyzed addition of dialkyl phosphites to mono- or difunctional aldehydes or ketones (F. Texier-Boullet, A. Foucaud, Synthesis, 1982, 916): 
Specifically, as a result of reacting diethyl phosphite with benzaldehyde, (1-hydroxy-1-phenyl)-methylphosphonic acid diethyl ester is obtained: 
The protection group is preferably eliminated by hydrolytic clearage through silylation with trialkylsilyl halides, e.g. trimethylsilyl chloride/(NaI or NaBr), and subsequent reaction with alcohols or water (S. Freeman, J. Chem. Soc., Perkin Trans. 2, 1991, 263).
The acrylophosphonic acids AP according to the invention of formula (I) (Xxe2x95x90CONR3, n=1) can be prepared by reaction of dialkoxyphosphoryl acrylic acids DPA with monofunctional amines in the presence of a suitable condensing agent and subsequent hydrolysis of the phosphonic acid ester groups. 
Carbodiimides or phosphoroxychlorides (Houben-Weyl, Vol. 15/2, Peptide; 4th Edition, Georg Thieme Verlag, Stuttgart 1974, pp. 103 et seq and 232 et seq) can be used as condensing agent for the amidation. The elimination of the phosphonic acid ester groups is carried out by means of trimethylsilyl bromide.
By way of example, the reaction of 2-[4-(dimethoxyphosphoryl)-2-oxabutyl]-acrylic acid with diethylamine via 2-[4-(dimethoxyphosphoryl)-2-oxabutyl]-acrylic acid diethylamide gives the corresponding acrylamidophosphonic acid {2-[4-(dihydroxyposphoryl)-2-oxabutyl]-acrylic acid diethylamide}: 
The dialkoxyphosphoryl-acrylic acids DPA used can be prepared from the corresponding dialkoxyphosphoryl-acrylic acid alkyl esters DPAE (cf. N. Moszner, F. Zeuner, U. K. Fischer, V. Rheinberger, Macromol. Chem. Phys. 200 (1999) by selective alkaline hydrolysis, e.g.: 
Specifically, the reaction of 2-[4-(dimethoxyphosphoryl)-2-oxabutyl]-acrylic acid ethyl ester with sodium hydroxide with elimination of ethanol gives 2-[4-(dimethoxyphosphoryl)-2-oxa-butyl]-acrylic acid: 
Analogously the amidation of dialkoxyphosphoryl acrylic acids with diamines results in acrylophosphonic acids according to the invention of formula (I) with Xxe2x95x90CONR3 and n=2: 
By way of example, the reaction of 2-[4-(dimethoxyphosphoryl)-2-oxa-butyl]-acrylic acid with ethylenediamine gives N,Nxe2x80x2-bis-[(6-dimethoxyphosphoryl)-4-oxa-2-methylene-hexanoyl]-ethylenediamine, which can be transformed by treatment with trimethylsilyl bromide into N,Nxe2x80x2-bis-[(6-dihydroxyphosphoryl)-4-oxa-2-methylene-hexanoyl]-ethylenediamine: 
Preferred examples of acrylophosphonic acids according to the invention of formula (I) are i.a.: 
The acrylophosphonic acids according to the invention are practically completely hydrolysis-stable at room temperature. They are therefore suitable in particular for use with aqueous mixtures.
Moreover, the acrylophosphonic acids according to the invention are characterized, compared with the corresponding carboxylic acid derivatives (Xxe2x95x90COO, Zxe2x95x90H), by a much better solubility in polar organic solvents such as e.g. ethanol, acetone, methylene chloride or ethyl acetate. In addition, they are largely inert vis-a-vis other compounds such as e.g. organic solvents, while by way of example the corresponding carboxylic acid esters (Xxe2x95x90COO, Zxe2x80x94alkyl radical) already have a tendency towards alcoholysis at room temperature in the presence of ethanol.
Due to the presence of polymerizable groups, the acrylophosphonic acid esters according to the invention are suitable as starting materials for the preparation of polymers and copolymers. They can be homopolymerized with the known methods of radical polymerisation or copolymerized e.g. with suitable comonomers.
To carry out the polymerisation, the known radical initiators (cf. Encyclopedia of Polymer Science and Engineering, Vol. 13, Wiley-Interscience Publisher, New York 1988, 754 et seq) can be used. Azo compounds, such as azobis(isobutyronitrile) (AIBN) or azobis-(4-cyanovalerianic acids) or peroxides, such as dibenzoylperoxide, dilauroylperoxide, tert.-butylpercotoate, tert.-butylperbenzoate or di.-(tert.-butyl)peroxide are particularly suitable.
Benzopinacol and 2,2xe2x80x2-dialkylbenzopinacols are also suitable as initiators for hot-curing.
Furthermore, photoinitiators (cf. J. P. Fouassier, J. F. Rabek (Ed.), Radiation Curing in Polymer Science and Technology, Vol. II, Elsevier Applied Science, London and New York 1993) can also be used for polymerisation with UV light or light of visible wavelengths, such as benzoinethers, dialkylbenzilketals, dialkoxyacetophenones, acylphosphinic oxides, xcex1-diketones, such as 9,10-phenanthrenequinone, diacetyl, furil, anisil, 4,4xe2x80x2-dichlorobenzil and 4,4xe2x80x2-dialkoxybenzil, and camphorquinone
The acrylophosphonic acids according to the invention can be used in particular as a component of adhesives, cements, composites and molded articles as well as, preferably, dental materials. The compounds according to the invention can also be used in polymerized or partly polymerized form i.e. in the form of polymers such as homo- or copolymers, for example as a component of glass ionomer cements.
The acrylophosphonic acids according to the invention can be polymerized alone or in a mixture with conventional radically polymerizable comonomers, in particular with difunctional crosslinking monomers. Cross-linking bi- or multifunctional acrylates or methacrylates, such as e.g. bisphenol-A-di-(meth)acrylate, bis-GMA (the addition product of methacrylic acid and bisphenol-A-diglycidyl ether), UDMA (the addition product of hydroxyethyl methacrylate and 2,2,4-trimethylhexamethylene diisocyanate), di-, tri- or tetraethylene glycol di(meth)acrylate, trimethylolpropantri(meth)acrylate and pentaerythritol tetra(meth)acrylate above all are suitable for the preparation of adhesives or dental materials. Butane diol di(meth)acrylate, 1,10-decane diol di(meth)acrylate and 1,12-dodecanediol di(meth)acrylate which are accessible by esterifying (meth)acrylic acid with the corresponding diols are also suitable.
The acrylophosphonic acids according to the invention can be used in free form or in the form of their salts, i.e. as phosphonates or phosphonate esters. In case of the alkali-metal ions, in particular sodium and lithium ions, as well as organic ammonium ions, in particular those derived from amine accelerators such as N,N-dihydroxyethyl-p-toluidine, N,N-bis-(2-hydroxy-3-methacryloxypropyl-3,5-xylidine or 4-(dimethylamino)-benzoic acid-2-ethyl-hexylester are preferably used as counterions. Amine accelerators are used in the field of dentistry as a component for example of photoinitiator systems. In general they are tert. amines which can act as H-donators and thus accelerate radical generation (cf. L. A. Linden, xe2x80x9cPhotocuring of Polymeric Dental Materials and Plastic Composite Resinsxe2x80x9d in Radiation Curing in Polymer Science and Technology, Vol. IV, J. P. Fouassier, J. F. Rabek (Editors), Elsevier Appl. Sci., London, New York 1993, 396 et seq).
Moreover, the acrylophosphonic acids according to the invention or their mixtures with other radically polymerizable comonomers can be filled with organic or inorganic particles or fibres to improve the mechanical properties. Preferred inorganic particulate fillers are amorphous spherical materials based on mixed oxides of SiO2, ZrO2 and/or TiO2, microfine fillers, such as pyrogenic silicic acid or precipitation silicic acid, as well as macro- or minifillers, such as quartz, glass ceramic or glass powders with an average particle size of 0.01 to 5 xcexcm. Furthermore, x-ray opaque fillers, such as ytterbium trifluroide, or glass fibres, polyamide or carbon fibres can also be used.
If necessary, further components can be added to the acrylophosphonic acids or mixtures thereof, above all solvents, such as water, methanol, ethanol, isopropanol, methyl ethyl ketone, acetone, ethyl acetate, dimethylformamide, dimethyl sulfoxide or mixtures thereof, as well as stabilisers, UV-absorbers, dyes, pigments or lubricants. Water, ethanol, acetone and ethyl acetate as well as mixtures thereof are preferred as solvents for use in dental materials.
The acrylophosphonic acids according to the invention are suitable in particular as a component of dental materials, such as fixing cements and filler composites and above all dental adhesives. Such materials are characterized by a very good adhesion to different substrates, such as hard tooth substance and metallic substrates, and are hydrolysis-stable under moist conditions.
Preferred dental materials according to the invention contain the following components (a), (b), (c), (d) and/or (e):
(a) 0.5 to 99 wt.-%, preferably 10 to 80 wt.-% and particularly preferably 20 to 50 wt.-% of one or more acrylophosphonic acids according to the invention,
(b) 0.01 to 5 wt.-% and preferably 0.1 to 2.0 wt.-% of radical initiators,
(c) 0 to 80 wt.-%, preferably 0 to 60 wt.-% and particularly preferably 0 to 50 wt.-% radically polymerizable comonomers,
(d) 0 to 95 wt.-%, preferably 0 to 80 wt.-% and particularly preferably 0 to 70 wt.-% solvents, in particular water, ethanol, acetone, ethyl acetate or mixtures thereof as well as mixtures of water with the named organic solvents,
(e) 0 to 90 wt.-%, particularly preferably, depending on the application, 0 to 20 wt.-% (adhesive), 20 to 60 wt.-% (cement) and 60 to 85 wt.-% (filling composite) filler.
According to a particularly preferred embodiment, the dental materials according to the invention are free from acrylo-phosphonic acids such as are described by e.g. way of example in DE 197 46 708.
The invention is explained in more detail in the following using examples.